A Fluorescent Protein Kinase C Inhibitor: 1-(1-Hydroxy-5-isoquinolinylsulfonyl)piperazine

Abstract

The isoquinolinesulfonamide compound 1-(5-isoquinolinyl-sulfonyl)-2-methyl-piperazine (H-7) has been widely used as a protein kinase C inhibitor. Although H-7 and its derivatives are useful for the demonstration of the biological function of protein kinase C or cyclic nucleotide-dependent protein kinases, these compounds are not available for a histological approach to protein kinase C. In the present study, we introduce 1-(1-hydroxy-5-isoquinolinylsulfonyl)piperazine (hydroxy H-7) as a useful tool in tissue experiments. The property of the compound as a protein kinase C inhibitor was similar to that of H-7. Hydroxy H-7 inhibited the enzyme in a competitive manner with ATP, the K₁ value was 23 μM, and exhibited a fluorescence property with a maximum emission wavelength of 444 nm excited at 350 nm. Fluoromicroscopical investigations revealed that hydroxy H-7 penetrated the cell membrane and was distributed mainly in the cytoplasm.